Rheumatoid arthritis (RA) is an autoimmune disease which is associated with a characteristic pattern of abnormal cellular and humoral immune response to Epstein-Barr virus (EBV). RA also shows a statistical association with the human Ia antigen, HLA-DR4. Since the abnormal EBV responses in RA appear to be due, in part, to abnormal T4+ helper/inducer cell function, we will study this subset of T cells by T cell cloning technology. We will isolate and characterize EBV-specific T cell clones from RA patients and compare them to similar clones from normal, healthy individuals. Since these T cell clones will be homogeneous cell populations derived from single cells, differences between RA and normals at the whole lymphocyte level will be greatly magnified. Potential differences between RA and normal clones which will be examined include 1) specificity for particular EBV determinants 2) Ia restriction patterns 3) ability to regulate B cell transformation 4) ability to produce lymphokines and 5) surface marker phenotype. Since EBV-reactive T cell clones from HLA-DR4 RA patients are such a restricted population of cells, we will attempt to make clonally-specific monoclonal antibodies (mcAbs) against these T cell clones. We will examine whether these clonally-specific antibodies can modify the EBV responses of patients' lymphocytes in vitro. In addition, we will examine the lymphocytes of other, unrelated RA patients to see whether these mcAbs can identify a shared "T cell idiotype" common to RA. Such clonally-specific mcAbs may have diagnositc and immunotherapeutic potential.